Figure 2.

The involvement of the CB₁, CB₂ receptors and PPARγ in the effect of the Sativex®-like phytocannabinoid combination. To determine the receptors involved in the beneficial effects of Sativex, we administered Δ⁹-THC-BDS (5 mg·kg⁻¹) together with a selective antagonist for the CB₂ receptor (AM630, 2 mg·kg⁻¹) and an antagonist of the CB₁ receptor (AM251, 2 mg·kg⁻¹). CBD-BDS (5 mg·kg⁻¹) was administered in combination with a PPARγ receptor antagonist (T0070907, 5 mg·kg⁻¹) for 10 days once the symptomatology had been established and motor function was evaluated by measuring horizontal activity (HACTV) on day 80 post-infection. The positive effect of Δ⁹-THC-BDS was significantly blocked by the administration of the CB₁ receptor antagonist and less so by the CB₂ receptor antagonist (A). Likewise, the beneficial effect of CBD-BDS was significantly attenuated by the antagonist of PPARγ (B). Activity parameters were recorded for 10 min and the results represent the mean ± SEM of six mice per group: ***P ≤ 0.001 versus Sham; #P ≤ 0.05 ###P ≤ 0.001 versus TMEV-VEH animals; ⋆P ≤ 0.05 versus TMEV-THC-BDS; ⋆⋆⋆P ≤ 0.001 versus TMEV-Δ⁹-THC-BDS; versus TMEV-CBD-BDS; ^**P ≤ 0.01 TMEV-THC-BDS-AM630 versus TMEV-THC-BDS-AM251 (one-way anova followed by Tukey's and Bonferroni's test: CBD-BDS and antagonist analysis; non-parametric Kruskal–Wallis test: Δ⁹-THC-BDS and antagonist analysis). ns, not significant.